Serial Noninvasive In Vivo Positron Emission Tomographic Tracking of Percutaneously Intramyocardially Injected Autologous Porcine Mesenchymal Stem Cells Modified for Transgene Reporter Gene Expression

Background-Porcine bone marrow-derived mesenchymal stem cells (MSCs) were stably transfected with a lentiviral vector for transgene expression of the trifusion protein renilla luciferase, red fluorescent protein and herpes simplex truncated thymidine kinase (LV-RL-RFP-tTK; positron emission tomography [PET] reporter gene) for in vivo noninvasive tracking of the intramyocardially delivered MSC fate. Methods and Results-A closed-chest, reperfused myocardial intarction was created in farm pigs. Sixteen days after myocardial infarction, LV-RL-RFP-tTK-MSCs were injected intramyocardially using electromechanical mapping guidance in the infarct border zone (n=7). PET-computed tomographic metabolic and perfusion imaging was performed after an intravenous injection of 10 mCi [18F]-FHBG and 13N-ammonia PET at 30 +/- 2 hours and 7 days after LV-RL-RFP-tTK-MSC treatment. Fusion imaging of the [18F]-FHBG PET-computed tomography with MRI was used to determine the myocardial location of the injected LV-RL-PFP-tTK-MSCs. Seven days after injections, [18F]-FHBG PET showed a decreased cardiac uptake with a mild increased pericardial and pleura uptake in the treated animals, which was confirmed by the measurement of luciferase activity. At 10 days, infarct size by MRI in the LV-RL-RFP-tTK-MSC-treated animals was smaller than controls (n=7) (23.3 +/- 1.5% versus 30.2 +/- 3.5%, P<0.005). The presence of the LV-RL-RFP-tTK-MSCs (5.8 +/- 1.1% of the injected cells) in the myocardium 10 days after intramyocardial delivery was confirmed histologically. Conclusions-Reporter gene imaging enables the tracking of the persistence of viable LV-RL-RFP-tTK-MSC in the peri-infarcted porcine myocardium at 10 days after delivery using clinical PET scanners. (Circ Cardiovasc Imaging. 2008;1:94-103.)